BMC Evolutionary Biology

BioMed Central

Open Access

Software

BEAST: Bayesian evolutionary analysis by sampling trees

Alexei J Drummond*1,2 and Andrew Rambaut3
Address: 1Bioinformatics Institute, University of Auckland, Auckland, New Zealand, 2Department of Computer Science, University of Auckland,
Auckland, New Zealand and 3Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, UK
Email: Alexei J Drummond* - alexei@cs.auckland.ac.nz; Andrew Rambaut - a.rambaut@ed.ac.uk
* Corresponding author

Published: 8 November 2007

BMC Evolutionary Biology 2007, 7:214

doi:10.1186/1471-2148-7-214

Received: 16 October 2007

Accepted: 8 November 2007

This article is available from: http://www.biomedcentral.com/1471-2148/7/214

2007 Drummond and Rambaut; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Background: The evolutionary analysis of molecular sequence variation is a statistical enterprise.
This is reflected in the increased use of probabilistic models for phylogenetic inference, multiple
sequence alignment, and molecular population genetics. Here we present BEAST: a fast, flexible
software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree.
A large number of popular stochastic models of sequence evolution are provided and tree-based
models suitable for both within- and between-species sequence data are implemented.
Results: BEAST version 1.4.6 consists of 81000 lines of Java source code, 779 classes and 81
packages. It provides models for DNA and protein sequence evolution, highly parametric
coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical
alignment and a wide range of options for prior distributions. BEAST source code is objectoriented, modular in design and freely available at http://beast-mcmc.googlecode.com/ under the
GNU LGPL license.
Conclusion: BEAST is a powerful and flexible evolutionary analysis package for molecular
sequence variation. It also provides a resource for the further development of new models and
statistical methods of evolutionary analysis.

Background
Evolution and statistics are two common themes that pervade the modern analysis of molecular sequence variation. It is now widely accepted that most questions
regarding molecular sequences are statistical in nature and
should be framed in terms of parameter estimation and
hypothesis testing. Similarly it is evident that to produce
models that accurately describe molecular sequence variation an evolutionary perspective is required.
The BEAST software package is an ambitious attempt to
provide a general framework for parameter estimation
and hypothesis testing of evolutionary models from

molecular sequence data. BEAST is a Bayesian statistical

framework and thus provides a role for prior knowledge
in combination with the information provided by the
data. Bayesian Markov chain Monte Carlo (MCMC) has
already been enthusiastically embraced as the state-of-theart method for phylogenetic reconstruction, largely driven
by the rapid and widespread adoption of MrBayes [1].
This enthusiasm can be attributed to a number of factors.
Firstly, Bayesian methods allow the relatively straightforward implementation of extremely complex evolutionary
models. Secondly, there is an often erroneous perception
that Bayesian estimation is "faster" than heuristic optimization based on a maximum likelihood criterion.

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In addition to phylogenetic inference, a number of

researchers have recently developed Bayesian MCMC software for coalescent-based estimation of demographic
parameters from genetic data [2-7]. Like phylogenetic
analysis, these also require a gene tree in the underlying
model, although in this setting, the sequences represent
different individuals from the same species, rather than
from different species. Most recently, Bayesian MCMC has
also been applied to a central problem in evolutionary
bioinformatics: the co-estimation of phylogeny and
sequence alignment [8,9]. Taken together with progress in
phylogenetics and coalescent-based population genetics,
Bayesian MCMC has been applied to most of the evolutionary questions commonly asked of molecular data.
BEAST can be compared to a number of other software
packages with similar goals, such as MrBayes [1], which
currently focuses on phylogenetic inference and Batwing
[4] which focuses predominantly on coalescent-based
population genetics of microsatellites. Like these software
packages, the core algorithm implemented in BEAST is
Metropolis-Hastings MCMC [10,11]. MCMC is a stochastic algorithm that produces sample-based estimates of a
target distribution of choice. For our purposes the target
distribution is the posterior distribution of a set of evolutionary parameters given a set of molecular sequences.
Possibly the most distinguishing feature of BEAST is its
firm focus on calibrated phylogenies and genealogies, that
is, rooted trees incorporating a time-scale. This is achieved
by explicitly modeling the rate of molecular evolution on
each branch in the tree. On the simplest level this can be
a uniform rate over the entire tree (i.e., the molecular
clock model [12]) with this rate known in advance or estimated from calibration information. One of the most
promising recent advances in molecular phylogenetics
has been the introduction of relaxed molecular clock models that do not assume a constant rate across lineages [1320]. BEAST was the first software package that allows
inference of the actual phylogenetic tree under such models [21].
The purpose behind the development of BEAST is to bring
a large number of complementary evolutionary models
(substitution models, insertion-deletion models, demographic models, tree shape priors, relaxed clock models,
node calibration models) into a single coherent framework for evolutionary inference. This building-block principle of constructing a complex evolutionary model out of
a number of simpler model components provides powerful new possibilities for molecular sequence analysis. The
motivation for doing this is (1) to avoid the unnecessary
simplifying assumptions that currently exist in many evolutionary analysis packages and (2) to provide new model
combinations and a flexible system for model specifica-

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tion so that researchers can tailor their evolutionary analyses to their specific set of questions.
The ambition of this project requires teamwork, and we
hope that by making the source code of BEAST freely
available, the range of models implemented, while
already large, will continue to grow and diversify.

Results and Discussion

BEAST provides considerable flexibility in the specification of an evolutionary model. For example, consider the
analysis of a multiple sequence alignment of coding DNA.
In a BEAST analysis, it is possible to allow each codon
position to have a different substitution rate, a different
amount of rate heterogeneity among sites, and a different
amount of rate heterogeneity among branches, whilst
sharing the same intrinsic ratio of transitions to transversions with the other codon positions. In fact, any or all
parameters (including the tree itself) can be shared or
independent among partitions of the sequence data.
An unavoidable feature of Bayesian statistical analysis is
the specification of a prior distribution over parameter
values. This requirement is both an advantage and a burden. It is an advantage because relevant knowledge such
as palaeontological calibration of phylogenies is readily
incorporated into an analysis. However, when no obvious
prior distribution for a parameter exists, a burden is
placed on the researcher to ensure that the prior selected
is not inadvertently influencing the posterior distribution
of parameters of interest.
In BEAST, all parameters (whether they be substitutional,
demographic or genealogical) can be given informative
priors (e.g. exponential, normal, lognormal or uniform
with bounds, or combinations of these). For example, the
age of the root of the tree can be given an exponential
prior with a pre-specified mean.
The model of evolution
The evolutionary model for a set of aligned nucleotide or
amino acid sequences in BEAST is divided into five components. For each of these a range of possibilities are
offered and thus a large number of unique evolutionary
models can easily be constructed. These components are:

Substitution model The substitution model is a homogeneous Markov process that defines the relative rates at
which different substitutions occur along a branch in the
tree.
Rate model among sites The rate model among sites
defines the distribution of relative rates of evolutionary
change among sites.

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Rate model among branches The rate model among

branches defines the distribution of rates among branches
and is used to convert the tree, which is in units of time,
to units of substitutions. These models are important for
divergence time estimation procedures.
Tree a model of the phylogenetic or genealogical relationships of the sequences.
Tree prior The tree prior provides a parameterized
prior distribution for the node heights (in units of time)
and tree topology.
Substitution models and rate models among sites
For nucleotide data, all of the models that are nested in
the general time-reversible (GTR) model [22,23] -including the well known HKY85 model [24] can be specified.
For the analysis of amino acid sequence alignments any of
the following replacement models can be used:
Blosum62, CPREV, Dayhoff, JTT, MTREV and WAG.
When nucleotide data represents a coding sequence (i.e.
an in-frame protein-coding sequence with introns
removed) the Goldman and Yang model [25] can be used
to model codon evolution. In addition, -distributed rates
among sites [26,27] or a proportion of invariant sites, or
a combination of the two [28,29] can be used to describe
rate heterogeneity among sites.
Rate models among branches, divergence time estimation
and time-stamped data
The basic model for rates among branches supported by
BEAST is the strict molecular clock model [12], calibrated
by specifying either a substitution rate or the date of a
node or set of nodes. In this context, dates of divergence
for particular clades can be estimated. The clades can be
defined either by an enforced grouping of taxa or as the
most recent common ancestor of a set of taxa of interest.
The second alternative does not require monophyly of the
selected taxa with respect to the rest of the tree. Furthermore, when the differences in the dates associated with
the tips of the tree comprise a significant proportion of the
age of the entire tree, these dates can be incorporated into
the model providing a source of information about the
overall rate of evolutionary change [3,30,31].

In BEAST, divergence time estimation has also been

extended to include relaxed phylogenetics models, in which
the rate of evolution is allowed to vary among the
branches of the tree. In particular we support a class of
uncorrelated relaxed clock branch rate models, in which
the rate at each branch is drawn from an underlying distribution such as exponential or lognormal [21].

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prior. The units implied by the prior on the evolutionary

rate will determine the units of the node heights in the
tree (including the age of the most recent common ancestor) as well as the units of the demographic parameters
such as the population size parameter and the growth rate.
For example, if the evolutionary rate is set to 1.0, then the
node heights (and root height) will be in units of mutations per site (i.e. the units of branch lengths produced by
common software packages such as MrBayes 3.0). Similarly, for a haploid population, the coalescent parameter
will be an estimate of Ne, where Ne is the effective population size and is the rate of mutation per generation.
However, if, for example, the evolutionary rate is
expressed in mutations per site per year, then the branches
in the tree will be in units of years. Furthermore the population size parameter of the demographic model will
then be equal to Ne, where is the generation length in
years. Finally, if the evolutionary rate is expressed in units
of mutations per site per generation then the resulting tree
will be in units of generations and the population parameter of the demographic model will be in natural units
(i.e. will be equal to the effective number of reproducing
individuals, Ne).
Tree Priors
When sequence data has been collected from a homogenous population, various coalescent [32,33] models of
demographic history can be used in BEAST to model population size changes through time. At present the simple
parametric models available include constant size N(t) =
Ne (1 parameter), exponential growth N(t) = Nee-gt (2
parameters) and logistic growth (3 parameters).

In addition, the highly parametric Bayesian skyline plot

[34] is also available, but this model can only be used
when the data are strongly informative about population
history. All of these demographic models are parametric
priors on the ages of nodes in the tree, in which the hyperparameters (e.g., population size, Ne, and growth rate, g)
can be sampled and estimated. As well as performing single locus coalescent-based inference, two or more
unlinked gene trees can be simultaneously analyzed
under the same demographic model. Sophisticated multilocus coalescent inference can be achieved by allocating a
separate overall rate and substitution process for each
locus, thereby accommodating loci with heterogeneous
evolutionary processes.
At present there are only a limited number of options for
non-coalescent priors on tree shape and branching rate.
Currently a simple Yule prior on birth rate of new lineages
(1 parameter) can be employed. However, generalized
birth-death tree priors are under development.

If the sequence data are all from one time point, then the
overall evolutionary rate must be specified with a strong

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In addition to general models of branching times such as

the coalescent and Yule priors, the tree prior may also
include specific distributions and/or constraints on certain node heights and topological features. These additional priors may represent other sources of knowledge
such as expert interpretation of the fossil record. For
example, as briefly noted above, each node in the tree can
have a prior distribution representing knowledge of its
date. This method of calibrating a tree based on specifying
the date of one of the nodes has a long history [35]. A
recent paper on "relaxed phylogenetics" contains more
information on calibration priors [21].
Insertion-deletion models
Finally, BEAST also has a model of the insertion-deletion
process. This provides the ability to co-estimate the phylogeny and the multiple sequence alignment. Currently
only the TKF91 model of insertion-deletion [36] is available. Interested readers should refer to the paper on this
subject for more details [8].
Multiple data partitions and linking and unlinking
parameters
BEAST provides the ability to analyze multiple data partitions simultaneously. This is useful when combining multiple genes in a single multi-locus coalescent analysis (e.g.
[37]) or to allocate different evolutionary processes to different regions of a sequence alignment (such as the codon
positions; e.g. [6]). The parameters of the substitution
model, the rate model among sites, the rate model among
branches, the tree, and the tree prior can all be 'linked' or
'unlinked' in a analysis involving multiple partitions. For
example in an analysis of HIV-1 group O by Lemey et al
[37], three loci (gag, int, pol) were assumed to share the
same substitution model parameters (GTR), as well as
sharing the same demographic history of exponential
growth. However they were assumed to have different
shape parameters for -distributed rate heterogeneity
among sites, different rate parameters for the strict molecular clock and the three tree topologies and sets of divergence times were also assumed to be independent and
unlinked.
Model comparison and model selection
The most sound theoretical framework for model comparison in a Bayesian framework is calculation of the Bayes
factor (BF):

BF =

p(D|M1)
p(D|M2 )

(1)

where p(D|M) is the marginal likelihood of model M,

averaged over the model parameter values :

p(D | M) =

Pr(D | , M)p( | M)d

(2)

So the BF is the ratio of the marginal likelihoods of the

two models. Generally speaking calculating the BF
involves a reversible jump MCMC in which a Markov
chain is constructed that samples a state space containing
both models. Reversible jump MCMC has not been
implemented in BEAST yet. However there are a couple of
methods of approximating the marginal likelihood of a
model (and therefore the BF between two models) by
processing the output of a BEAST analysis. A simple
method first described by Newton and Raftery [38] computes the BF via importance sampling (with the posterior
as the importance distribution). With this importance distribution it turns out that the harmonic mean of the sampled likelihoods is an estimator of the marginal
likelihood:

m HM(D | M) = (

1
N

Pr(D|q1(i),M))

; q (i) ~ p(q | D, M)
(3)

This estimator does not always behave very well, but there
are number of modifications that can be used to stabilize
it and bootstrapping can be employed to assess the uncertainty in the estimated marginal likelihoods. In general, a
BF > 20 is strong support for the favoured model (M1 in
equation 1).
Example
We demonstrate some of the key features of a Bayesian
analysis on a sample of 17 dengue virus serotype 4
sequences, isolated at dates ranging from 1956 to 1994
(see [30] for details). Like many RNA viruses, dengue virus
evolves at a rapid rate and as a result the sampling times
of the 17 isolates can be used by BEAST as calibrations to
estimate the overall substitution rate and the divergence
times in years. We analyzed the data under both a codonposition specific substitution model (GTR + CP), in which
each codon position had a separate relative substitution
rate parameter, as well as the standard GTR + + I model.
Both of these models have the same number of free
parameters. We also investigated two different models of
rates variation among branches: the strict clock and the
uncorrelated lognormal-distributed relaxed molecular
clock. We used the constant population size coalescent as
the tree prior. For each model the MCMC was run for
10,000,000 steps and sampled every 500 steps. The first
100,000 steps of each run were discarded as burnin. This
resulted in effective sample sizes for the posterior probability of much more than 1000 for all four analyses, (see
Addiitional files 1,2,3,4, for BEAST XML input of all four
runs).
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As has been previously suggested to be generally the case

for protein-coding sequences [39], we found that the
codon-position-specific model of rate heterogeneity
among sites has a substantially superior fit to the data
than the GTR + + I model (see Table 1), and also supports a different consensus tree topology (see Figure 1).
However we find little difference (log BF = 0.8) between
the two models of rate variation among branches, indicating that this particular data can be treated as clock-like, as
has been previously suggested [30]. Under the strict clock
model with codon-position rate heterogeneity and a con-

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stant-size coalescent tree prior the estimated date of the

root of the phylogeny is 1924 (95% highest posterior density (HPD): 1911 1936) and the estimated rate of substitution for this serotype was estimated to be 8.38 10-4
(95% HPD: 6.40 10-4 1.05 10-3).
One method of summarizing the posterior distribution of
phylogenetic trees is to rank the tree topologies by posterior probability and consider the smallest set of trees that
represents at least x% of the posterior probability. This set
is termed the x% credible set of tree topologies [40]. For

Figure 1 tree of 17 dengue 4 env sequences

Consensus
Consensus tree of 17 dengue 4 env sequences The consensus tree for the example analysis of Dengue 4 sequences under
the strict clock analysis with a GTR + CP substitution model. Each internal node is labeled with the posterior probability of
monophyly of the corresponding clade. The gray bars illustrated the extent of the 95% highest posterior density intervals for
each divergence time. The scale is in years.

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Table 1: Summary of the four models analyzed

Substitution Model
(a) GTR + CP + strict
(b) GTR + CP + relaxed
(c) GTR + + I + strict
(d) GTR + + I + relaxed

Marginal Likelihood

50% credible set size

-3656.13 0.11
-3655.33 0.11
-3751.37 0.11
-3750.23 0.11

38
57
289
469

Mean tree height (years)

70.1 0.09
70.5 0.2
71.7 0.1
72.0 0.2

The marginal likelihoods, the number of distinct tree topologies in the 50% credible set and the mean tree height ( stderr) of the four substitution
models that were analyzed in the example. The large improvement in marginal likelihood clearly indicates that the two codon-position substitution
models (CP) are substantially superior to the models in which rate heterogeneity among sites is modeled by a 3-distribution and a proportion of
invariant sites. In contrast, in this example there is little difference in fit to the data between the strict clock and the relaxed clock analyses,
suggesting that this data is clock-like.

the purposes of hypothesis testing, a phylogeny can be

rejected if it is not found in the 95% credible set of tree
topologies. In this example we found that the size of the
credible sets varied substantially for the different models.
In table 1 we list posterior estimates of the size of the 50%
credible sets for each of the four models. We chose 50%
because both the GTR + + I models sampled many singleton trees in the tail of the distribution so that an accurate estimate of the size of the 95% credible set was not
feasible. Nevertheless the table clearly indicates that the
posterior distribution of the GTR + CP models is almost
an order of magnitude more concentrated in tree space.
This suggests that, for this data set, the GTR model is both
a more precise estimator and a better fit to the data. In the
case of the GTR + CP + strict model, 38 of the 1.1919
1017 rooted trees with 17 tips commanded half the total
probability given the data.

Conclusion
BEAST is a flexible analysis package for evolutionary
parameter estimation and hypothesis testing. The component-based nature of model specification in BEAST means
that the number of different evolutionary models possible
is very large and therefore diffcult to summarize. However
a number of published uses of the BEAST software already
serve to highlight the breadth of application the software
enjoys [6,8,34,37,41].
BEAST is an actively developed package and enhancements for the next version include (1) birth-death priors
for tree shape (2) faster and more flexible codon-based
substitution models (3) the structured coalescent to
model subdivided populations with migration (4) models of continuous character evolution and (5) new relaxed
clock models based on random local molecular clocks.

Methods
The overall architecture of the BEAST software package is
a file-mediated pipeline. The core program takes, as input,
an XML file describing the data to be analyzed, the models
to be used and technical details of the MCMC algorithm
such as the proposal distribution (operators), the chain

length and the output options. The output of a BEAST

analysis is a set of tab-delimited plain text files that summarize the estimated posterior distribution of parameter
values and trees.
A number of additional software programs assist in generating the input and analyzing the output:
BEAUti is a software package written in Java and distributed with BEAST that provides a graphical user interface
for generating BEAST XML input files for a number of simple model combinations.
Tracer is a software package written in Java and distributed separately from BEAST that provides a graphical tool
for MCMC output analysis. It can be used for the analysis
of the output of BEAST as well as the output of other common MCMC packages such as MrBayes [1] and BAli-Phy
[42].
Because of the combinatorial nature of the BEAST XML
input format, not all models can be specified through the
graphical interface of BEAUti. Indeed, the sheer number
of possible combinations of models mean that, inevitably, many combinations will essentially be untried and
untested. It is also possible to create models that are inappropriate or meaningless for the data being analyses.
BEAUti is therefore intended as a way of generating commonly used and well-understood analyses. For the more
adventurous researcher, and with the above warnings in
mind, the XML file can be directly edited. A number of
online tutorials are available to guide users on how to do
this.
One of the primary motivations for providing a highly
structured XML input format is to facilitate reproducibility
of complex evolutionary analyses. While an interactive
graphical user interface provides a pleasant user experience, it can be time-consuming and error-prone for a user
to record and reproduce the full sequence of choices that
are made, especially with the large array of options typically available for MCMC analysis. By separating the

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graphical user interface (BEAUti) from the analysis

(BEAST) we accommodate an XML layer that captures the
exact details of the MCMC analysis being performed. We
strongly encourage the routine publication of XML input
files as supplementary information with publication of
the results of a BEAST analysis. Because of the non-trivial
nature of MCMC analyses and the need to promote reproducibility, it is our view that the publication of the exact
details of any Bayesian MCMC analysis should be made a
pre-requisite for publication of all MCMC analysis results.

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years 2000 and 2002. Portions of the BEAST source code

are based on previous C++ software developed by AR.
Both authors contributed to the writing of this paper.

Additional material
Additional file 1
Dengue4-GTR-CP-strict. The BEAST input XML file for the GTR + CP
+ strict clock analysis.
Click here for file
[http://www.biomedcentral.com/content/supplementary/14712148-7-214-S1.xml]

The output from BEAST is a simple tab-delimited plain

text file format with one a row for each sample. When
accumulated into frequency distributions, this file provides an estimate of the marginal posterior probability
distribution of each parameter (e.g. parameters such as
mutation rate, tree height and population size). This can
be done using any standard statistics package or using the
specially written package, Tracer [43]. Tracer provides a
number of graphical and statistical ways of analyzing the
output of BEAST to check performance and accuracy. It
also provides specialized functions for summarizing the
posterior distribution of population size through time
when a coalescent model is used.

Additional file 2
Dengue4-GTR-CP-relaxed. The BEAST input XML file for the GTR +
CP + relaxed clock analysis.
Click here for file
[http://www.biomedcentral.com/content/supplementary/14712148-7-214-S2.xml]

Additional file 3

Dengue4-GTR-GI-strict. The BEAST input XML file for the GTR + +

I + strict clock analysis.
Click here for file
[http://www.biomedcentral.com/content/supplementary/14712148-7-214-S3.xml]

The phylogenetic tree of each sample state is written to a

separate file as either NEWICK or NEXUS format. This can
be used to investigate the posterior probability of various
phylogenetic questions such as the monophyly of a particular group of organisms or to obtain a consensus phylogeny.
Although there is always a trade-off between a program's
flexibility and its computational performance, BEAST performs well on large analyses (e.g. [41]). A Bayesian
MCMC algorithm needs to evaluate the likelihood of each
state in the chain and thus performance is dictated by the
speed at which these likelihood evaluations can be made.
BEAST attempts to minimize the time taken to evaluate a
state by only recalculating the likelihood for parts of the
model that have changed from the previous state. Furthermore, the core computational functions have been implemented in the C programming language. This can be
compiled into a highly optimized library for a given platform providing an improvement in speed. If this library is
not found, BEAST will use its Java version of these functions, thereby retaining its platform-independence.

Additional file 4

Dengue4-GTR-GI-relaxed. The BEAST input XML file for the GTR +

+ I + relaxed clock analysis.
Click here for file
[http://www.biomedcentral.com/content/supplementary/14712148-7-214-S4.xml]

Acknowledgements
We would like to thank Roald Forsberg, Joseph Heled, Philippe Lemey,
Gerton Lunter, Sidney Markowitz, Oliver Pybus, Beth Shapiro, Korbinian
Strimmer and Marc Suchard for invaluable contributions. AJD was partially
supported by the Wellcome Trust and AR was supported by the Royal
Society.

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the BEAST source code are based on an original Markov
chain Monte Carlo program developed by AJD (called
MEPI) during his PhD at Auckland University between the

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